Stem Cells from Human Exfoliated Deciduous Tooth-Derived Conditioned Medium Enhance Recovery of Focal Cerebral Ischemia in Rats

Inoue, Toshi; Shimada, Masahiko; Hattori, Hiroyuki; Wakita, Hideaki; Wakabayashi, Toshihiko; Ueda, Minoru

doi:10.1089/ten.tea.2011.0385

Cited by 138 publications

(109 citation statements)

References 21 publications

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“…We showed previously that SHED transplantation into completely transected rat spinal cord resulted in the functional recovery of hind limb locomotion (14). Moreover, SHED engraftment promotes functional recovery from various acute and chronic CNS insults through paracrine mechanisms that activate endogenous tissue-repairing activity (15,16). Furthermore, these studies showed that SHED-conditioned medium (SHED-CM) exerts similar therapeutic effects to those of SHEDs, including remyelination of the CNS.…”

Section: Ultiple Sclerosis (Ms) and Its Animal Model Experimental mentioning

confidence: 98%

Conditioned Medium from the Stem Cells of Human Exfoliated Deciduous Teeth Ameliorates Experimental Autoimmune Encephalomyelitis

Shimojima

Takeuchi

Jin

et al. 2016

The Journal of Immunology

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Multiple sclerosis (MS) is a major neuroinflammatory demyelinating disease of the CNS. Current MS treatments, including immunomodulators and immunosuppressants, do not result in complete remission. Stem cells from human exfoliated deciduous teeth (SHEDs) are mesenchymal stem cells derived from dental pulp. Both SHED and SHED-conditioned medium (SHED-CM) exhibit immunomodulatory and regenerative activities and have the potential to treat various diseases. In this study, we investigated the efficacy of SHED-CM in treating experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. EAE mice treated with a single injection of SHED-CM exhibited significantly improved disease scores, reduced demyelination and axonal injury, and reduced inflammatory cell infiltration and proinflammatory cytokine expression in the spinal cord, which was associated with a shift in the microglia/macrophage phenotype from M1 to M2. SHED-CM also inhibited the proliferation of myelin oligodendrocyte glycoprotein–specific CD4+ T cells, as well as their production of proinflammatory cytokines in vitro. Treatment of EAE mice with the secreted ectodomain of sialic acid–binding Ig-like lectin-9, a major component of SHED-CM, recapitulated the effects of SHED-CM treatment. Our data suggest that SHED-CM and secreted ectodomain of sialic acid–binding Ig-like lectin-9 may be novel therapeutic treatments for autoimmune diseases, such as MS.

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Section: Ultiple Sclerosis (Ms) and Its Animal Model Experimental mentioning

confidence: 98%

Conditioned Medium from the Stem Cells of Human Exfoliated Deciduous Teeth Ameliorates Experimental Autoimmune Encephalomyelitis

Shimojima

Takeuchi

Jin

et al. 2016

The Journal of Immunology

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“…They are thought to originate from the cranial neural crest, which expresses early markers for both MSCs and neuroectodermal stem cells (Gronthos et al, 2000;Miura et al, 2003; and can differentiate into functional neurons and oligodendrocytes under appropriate conditions (Arthur et al, 2008;Király et al, 2009;. Engrafting these DPSCs promotes functional recovery from various acute and chronic insults of the CNS through paracrine mechanisms that activate endogenous tissue-repairing activities (de Almeida et al, 2011;Leong et al, 2012;Taghipour et al, 2012;Inoue et al, 2013;Yamagata et al, 2013;Yamamoto et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Secreted Ectodomain of Sialic Acid-Binding Ig-Like Lectin-9 and Monocyte Chemoattractant Protein-1 Promote Recovery after Rat Spinal Cord Injury by Altering Macrophage Polarity

Matsubara¹,

Matsushita²,

Saito³

et al. 2015

J. Neurosci.

136

143

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Engrafted mesenchymal stem cells from human deciduous dental pulp (SHEDs) support recovery from neural insults via paracrine mechanisms that are poorly understood. Here we show that the conditioned serum-free medium (CM) from SHEDs, administered intrathecally into rat injured spinal cord during the acute postinjury period, caused remarkable functional recovery. The ability of SHED-CM to induce recovery was associated with an immunoregulatory activity that induced anti-inflammatory M2-like macrophages. Secretome analysis of the SHED-CM revealed a previously unrecognized set of inducers for anti-inflammatory M2-like macrophages: monocyte chemoattractant protein-1 (MCP-1) and the secreted ectodomain of sialic acid-binding Ig-like lectin-9 (ED-Siglec-9). Depleting MCP-1 and ED-Siglec-9 from the SHED-CM prominently reduced its ability to induce M2-like macrophages and to promote functional recovery after spinal cord injury (SCI). The combination of MCP-1 and ED-Siglec-9 synergistically promoted the M2-like differentiation of bone marrow-derived macrophages in vitro, and this effect was abolished by a selective antagonist for CC chemokine receptor 2 (CCR2) or by the genetic knock-out of CCR2. Furthermore, MCP-1 and ED-Siglec-9 administration into the injured spinal cord induced M2-like macrophages and led to a marked recovery of hindlimb locomotor function after SCI. The inhibition of this M2 induction through the inactivation of CCR2 function abolished the therapeutic effects of both SHED-CM and MCP-1/ED-Siglec-9. Macrophages activated by MCP-1 and ED-Siglec-9 extended neurite and suppressed apoptosis of primary cerebellar granule neurons against the neurotoxic effects of chondroitin sulfate proteoglycans. Our data suggest that the unique combination of MCP-1 and ED-Siglec-9 repairs the SCI through anti-inflammatory M2-like macrophage induction.

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“…Human SHEDs transplanted into completely transected adult rat spinal cord resulting in the functional recovery of hind limb locomotion (Sakai et al 2012). SHED engraftment promotes also functional recovery from several acute and chronic CNS injuries through paracrine mechanisms triggering endogenous tissue-repairing action (Inoue et al 2013;Yamagata et al 2013). In addition, SHED-conditioned medium (SHED-CM) was found to exert similar therapeutic activities to those of SHEDs, including remyelination of the CNS (Shimojima et al 2016).…”

Section: Dental Tissues-derived Mscsmentioning

confidence: 99%

The transplantation of mesenchymal stem cells derived from unconventional sources: an innovative approach to multiple sclerosis therapy

Giacoppo

Bramantı

Mazzon

2017

Arch. Immunol. Ther. Exp.

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Stem Cells from Human Exfoliated Deciduous Tooth-Derived Conditioned Medium Enhance Recovery of Focal Cerebral Ischemia in Rats

Cited by 138 publications

References 21 publications

Conditioned Medium from the Stem Cells of Human Exfoliated Deciduous Teeth Ameliorates Experimental Autoimmune Encephalomyelitis

Conditioned Medium from the Stem Cells of Human Exfoliated Deciduous Teeth Ameliorates Experimental Autoimmune Encephalomyelitis

Secreted Ectodomain of Sialic Acid-Binding Ig-Like Lectin-9 and Monocyte Chemoattractant Protein-1 Promote Recovery after Rat Spinal Cord Injury by Altering Macrophage Polarity

The transplantation of mesenchymal stem cells derived from unconventional sources: an innovative approach to multiple sclerosis therapy

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